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Biomedical subjects

M C Jones

Publications and source records attributed to M C Jones.

At least 91 records · Page 5Linked to original sources

Monoclonal antibodies to cultured human glomerular mesangial cells. I. Reactivity with haematopoietic cells and normal kidney sections.

The aim of this study was to produce monoclonal antibodies to cultured human glomerular mesangial cells in order to obtain specific markers for these cells and to aid the study of their function. Using standard monoclonal antibody techniques, 29 hybridomas producing antibodies directed to cultured mesangial cells were obtained. Most of these antibodies were not reactive with normal or neoplastic haematopoietic cell lines by flow cytometry. Fourteen of the 29 culture supernatants bound to various components of normal human kidney sections stained by the alkaline phosphatase/anti-alkaline phosphatase (APAAP) method. Ten of these supernatants reacted with components within the glomerulus, with six binding to the mesangium. These studies suggest that (1) mesangial cells in culture may show significant de-differentiation, because most supernatants which reacted with mesangial cells in culture did not do so in tissue sections; (2) antibodies reactive with haematopoietic cells may not detect the majority of immunogenic surface antigens on cells in tissues; and (3) some of the antibodies which we have produced may prove to be useful markers for mesangial cells in glomerular disease.

Animals↗

Effect of cyclosporin A on immunoglobulin class in patients receiving blood transfusions.

IgG antibodies detected by flow cytometry in sera from potential renal transplant recipients are associated with an increased number of rejection episodes and impaired graft function. Furthermore, cytotoxic antibodies may develop if pre-transplant blood transfusions are given to such patients. We have investigated the effect of cyclosporin A on the development of IgM and IgG antibodies detected by flow cytometry after blood transfusions in 16 previously untransfused dialysis patients. Eight (group 1) received three to five third-party blood transfusions at two weekly intervals and the remaining eight (group 2) received transfusions with concomitant cyclosporin A therapy (10 mg/kg/day). Sera obtained after each transfusion were tested using flow cytometry against lymphocytes from six normal donors. In all 462 serum/cell combinations were tested. Sera from six out of eight patients in group 1 showed IgG antibody activity following blood transfusions and none developed IgM antibodies alone. In contrast IgG antibody activity was detected in one serum sample from only one of the eight patients in group 2 (P less than 0.02); a further three patients developed IgM but not IgG antibody activity during the transfusion protocol. IgG antibodies were found in 25/228 serum/cell combinations in group 1 but in 1/234 in group 2 (P less than 0.001). The patient in group 2 who developed IgG antibodies in one serum/cell combination was known to have red cell autoantibodies. This IgG activity was removed by red cell absorption, suggesting that the autoreactive red cell antibody cross-reacted with lymphocytes. Cytotoxic antibodies were detected in two serum/cell combinations in group 1 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗

Cyclosporin A and the humoral response to blood transfusion in the rat: definition of antigens which suppress alloantibody formation.

1. Blood transfusions improve renal allograft survival rates, but may induce antibodies which are directed to class I major histocompatibility complex antigens and mediate hyperacute transplant rejection. A model to study the development of such antibodies was developed in inbred strains of rats. 2. The influence of transplantation antigens shared between an initial course of blood transfusions, given with cyclosporin A, and a subsequent antigenic challenge (blood transfusion), given without cyclosporin A, on alloantibody responses to class I major histocompatibility complex antigens was then investigated. 3. Cyclosporin A administration prevented the development of alloantibodies to class I major histocompatibility complex antigens during the initial transfusion period. 4. After the challenge transfusions, alloantibody responses to class I major histocompatibility complex antigens were suppressed when class I major histocompatibility complex or minor histocompatibility antigens were shared between the initial and final transfusions. 5. This suppression only extended to third party class I antigens when minor histocompatibility complex antigens were shared between the initial and final transfusions. Sharing of class I or class II antigens had no effect on alloantibody responses to third party class I antigens coexpressed on the same cell. 6. These studies suggest that cyclosporin A given with blood transfusions may prevent clinical sensitization while permitting the development of suppressor activity, mediated by shared minor histocompatibility complex determinants, to a broad range of potential donor antigens.

Animals↗

The effect of cyclosporin administered during a third-party blood transfusion protocol on humoral immune responses.

Antigen pre-treatment in animals undoubtedly prolongs graft survival. In man, however, routine pre-transplantation blood transfusions have recently become controversial, principally because of the adverse effect of transfusion-induced sensitisation on graft survival rates. We have monitored the effect of cyclosporin administered during a planned programme of third-party blood transfusions on the development of both cytotoxic and anti-idiotypic antibodies. A total of 24 patients were recruited to the study; ten received cyclosporin with blood transfusions (BT) (group 1), 14 received BT alone (group 2). Anti-HLA antibodies developed in 3 of 9 patients in group 1 and 8 of 12 patients in group 2 (P less than 0.05). Anti-idiotypic antibody activity was detectable in 9 of 9 patients in group 1 and 7 of 12 patients in group 2 (P less than 0.006). The mechanism by which cyclosporin can prevent an anti-HLA antibody response and promote an anti-idiotypic response is unclear.

Antibodies, Anti-Idiotypic↗

Reduction of sensitization induced by blood transfusion in the rat by monoclonal antibodies.

Primary and secondary alloantibody responses were monitored in (AOxPVG)F1 hybrid rats after three transfusions of DA blood; the initial transfusion was either untreated or pretreated with monoclonal antibody directed to class I antigens or other cell surface markers. Mean antibody activity in recipient sera against class I DA antigens was significantly decreased by pretreatment with the monoclonal antibodies. The most marked suppression was associated with pretreatment by antibodies to the four major nonoverlapping epitopes of the RT1Aa antigen. Subsequent transfusions of DA blood failed to stimulate a secondary response. Crossreactivity of the alloantibody reactivity with BDIX antigens was diminished by pretreating the transfusions with rat anti-RT1A antibodies and, to a lesser extent, with a mouse monoclonal antibody (OX-18) to a common class I determinant. Monoclonal antibody pretreatment had no effect on the humoral response to class II DA antigens. These studies indicate that blood transfusions pretreated with monoclonal antibodies induce a less-potent cytotoxic humoral immune response and that reactivity is most effectively suppressed by completely masking the class I antigen. This technique may prove of clinical value in preventing the sensitization caused by blood transfusions in potential transplant recipients.

Animals↗

Rice tungro disease is caused by an RNA and a DNA virus.

We present evidence that rice tungro spherical virus (RTSV) has a genome of polyadenylated single-stranded RNA of about 10 kb whereas rice tungro bacilliform virus (RTBV) contains double-stranded circular DNA. RTBV DNA has been mapped and shown to have two discontinuities, one in each strand, at specific sites; it thus resembles that of the caulimoviruses. Gel electrophoresis of RTSV preparations revealed two protein bands (Mr 35K and 26K). RTBV yielded two major protein bands of 37K and 33K together with several minor species of higher and lower Mr which react with antiviral serum.

Capsid↗

Hepatoblastoma characterized by trisomy 20 and double minutes.

Karyotypic study of two hepatoblastomas revealed trisomies for chromosome 20 and the presence of double minutes (dmin). These cases are the second and third examples of trisomy 20 in hepatoblastoma and are the first examples of dmins in this rare childhood tumor.

Carcinoma, Hepatocellular↗

The otolaryngologic manifestations of Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease is a condition of central nervous system dysmyelination. We describe a familial series in which both otologic and laryngologic abnormalities were present. The diagnosis of this invariably fatal disorder can be made on a clinical and/or pathologic basis. As the otolaryngologic manifestations are often the first to appear, the consulting head and neck surgeon may be essential in the initial diagnosis of this hereditary disease.

Audiometry, Evoked Response↗

Patterns of malformation in children with congenital diaphragmatic defects.

The medical records of 102 live-born children with a congenital diaphragmatic defect were reviewed to determine the frequency and nature of underlying chromosomal, genetic, and nongenetic patterns of malformation. Overall, 40 children (39%) had a major nonpulmonary malformation, and 14 of these children (14%) had a previously recognized pattern of malformation. A group of 18 children (18%) with cardiac anomalies had an increased mortality rate in comparison with those children without cardiac defects (72% vs 38%). The frequency and severity of nonpulmonary abnormalities in children with congenital diaphragmatic defects suggest that examination of affected children should include cardiac evaluation, a karyotype when the defect is one feature of a broader pattern of altered development, and a careful evaluation for minor anomalies, which may provide clues to an overall diagnosis.

Abnormalities, Multiple↗

Community defibrillation in the Scottish Highlands.

Prompt defibrillation after cardiac arrest is necessary to save life. Inexpensive systems providing defibrillation facilities in the community of the Highlands have been devised, one for Inverness town practices, and one for rural practices. Both systems work by 'blind' defibrillation, once the clinical diagnosis of cardiac arrest is confirmed. Acute anti-arrhythmic drugs and intravenous infusions were not available. The systems functioned satisfactorily with general acceptance by the general practices concerned.

Attitude of Health Personnel↗

The neurocristopathies: reinterpretation based upon the mechanism of abnormal morphogenesis.

This review sets forth a broadened interpretation of the neurocristopathies based on the current understanding of the role of neural crest cells in normal development. Two general types of cristopathies are defined predicated on the abnormal mechanism involved in production of the defect or condition. Defects and disorders which constitute the originally defined neurocristopathies including pheochromocytoma, neurofibromatosis, and the multiple endocrine adenomatoses are best explained as dysplasias of neural crest derivatives. Affected individuals rarely exhibit true malformation of structure but do carry a lifetime risk for disordered growth of crest derived tissue. On the other hand, defects and disorders which derive from migrational abnormalities primarily of cranial neural crest cells such as frontonasal dysplasia, the DiGeorge sequence, and Waardenberg syndrome represent true malformations. The spectrum of involvement is usually definable at the time of diagnosis and disordered growth of crest derived tissue does not occur. The clinical implications of this distinction are discussed.

Cell Differentiation↗

Interstitial deletion of chromosome 22 in a patient with the DiGeorge malformation sequence.

We describe a chromosome 22 deletion in a patient with the DiGeorge malformation sequence as manifested by an interrupted aortic arch, mild thymic hypoplasia, and minor craniofacial anomalies. Although others have reported DiGeorge sequence patients with deletions derived from unbalanced translocations involving the chromosome 22 long arm, the small interstitial deletion described here appears to be unusual for patients with this disorder.

Aorta, Thoracic↗

Chromosome 10qter deletion syndrome: a review and report of three new cases.

We report on three patients with terminal deletions of chromosome 10q and compare them to 15 previously reported patients. A similar facial appearance with a prominent beaked nose, large and/or malformed ears, and a pattern of major abnormalities including severe mental retardation, cardiac anomalies, and anogenital anomalies are reviewed. We feel the manifestations of del 10qter are sufficiently distinct to suggest this diagnosis on clinical examination.

Abnormalities, Multiple↗

A sequential study of the peripheral nervous system involvement in experimental Chagas' disease.

To search for the sequential compromise of the spinal cord, nerves, and skeletal muscle in mice chronically infected with Trypanosoma cruzi, animals were subjected to electromyographic investigation, end-plate recordings, and histological studies at 7, 15, 37, 60, 90, 120, 180, 270, and 360 days postinfection. Electromyographic studies showed signs of motor unit remodeling as early as 15 days postinfection, when diminished duration and amplitude of motor unit potentials pointing to a primary muscle involvement were found. Thereafter, certain features of denervation, reinnervation, and primary muscle involvement were often found to coexist. Low miniature end-plate potentials with normal frequency and acetylcholine quantum content were found in end-plate recordings made at the phrenic-diaphragm in vitro. Double end-plate potentials were observed in most of the tested muscle fibers from day 90 postinfection. All these features suggest post-synaptic damage of the end-plate and the presence of reinnervation after day 90 postinfection. Histological studies disclosed inflammatory infiltrates consisting of lymphocytes and macrophages, with vasculitis as the main lesion in the hamstring muscles; intracellular parasites were seen in 25% of the cases. Neuropathic features, as expressed by type fiber grouping and grouped muscle fiber atrophy, were found. On nerve examination epineural, perineural, and endoneural vasculitis were seen. Digestion chambers and myelin ovoids (axonal degeneration) were observed. In teased fiber preparations, segmental internodal and paranodal demyelination and remyelination were found. The lumbar inflammatory spinal cord failed to show grey or white matter infiltrates. However, spinal roots and dorsal root ganglia were densely affected by inflammatory cells.

Animals↗